Endocrine therapy is one of the main systemic treatments for breast cancer. The basic drugs of endocrine therapy for breast cancer are anti-estrogens, aromatase inhibitors, luteinizing hormone-releasing hormone analogs, estrogen/androgen analogs and progestins.
1. Anti-estrogens, which bind to estrogen receptors and block the action of estrogen on the receptors. The most commonly used is triamcinolone acetonide, which can be used for the relief treatment of recurrent metastatic breast cancer, postoperative adjuvant therapy and breast cancer prevention in high-risk healthy women.
2.Aromatase inhibitors, by inhibiting the activity of aromatase, blocking the conversion of androstenedione and testosterone to estrogen via aromatization in tissues other than the ovary, so as to inhibit the growth of breast cancer cells and treat tumors.
3.LH-RH analog, through negative feedback action on hypothalamus, inhibits hypothalamus from producing gonadotropin-releasing hormone; it also competes with GnRH receptor or LHRH receptor on pituitary cell membrane to prevent pituitary from producing FSH and LH, thus reducing ovarian secretion of estrogen.
4.Androgens and estrogens. Therapeutic doses of androgens and estrogens can change the body’s endocrine environment and inhibit the growth of tumor cells, but they also show obvious adverse effects, and are currently used less clinically.
5. Progestins, through changing the body’s endocrine environment, inhibit the production of LH and ACTH by the pituitary gland through negative feedback, or act on breast cancer cells through progesterone receptors. The commonly used ones are megestrol and megestrol.
Endocrine therapy for recurrent metastatic breast cancer is aimed at improving the quality of life and prolonging the survival of patients. Whether to choose endocrine therapy for recurrent metastatic breast cancer depends on the hormone receptor status of the patient’s tumor tissue, age, menstrual status and the degree of disease progression. In principle, chemotherapy should be preferred for patients with rapidly progressing recurrent metastatic disease, while endocrine therapy can be preferred for slowly progressing hormone-responsive breast cancer, which used to be called hormone-dependent breast cancer.
Characteristics of recurrent metastatic breast cancer with slow progression.
1. Hormone receptor positivity.
2. longer disease-free survival after surgery.
3. only soft tissue and bone metastases, or asymptomatic visceral metastases such as non-diffuse pulmonary and liver metastases, other visceral metastases with small tumor load that are not life-threatening.
The hormone-responsive breast cancer concept, which defines which patients are suitable for endocrine therapy in terms of their potential benefit from endocrine therapy, considers patients who meet one or more of the following conditions to be likely to benefit from endocrine therapy
1. positive ER and/or PR at the primary site and/or recurrent metastases.
2, elderly patients.
3, long postoperative disease-free interval.
4, Previous benefit from previous endocrine therapy.
Basic principles of endocrine therapy for recurrent metastatic breast cancer.
1. The principle of treatment for recurrent metastatic breast cancer is to control the disease progression and improve the patient’s quality of life, so avoid unnecessary intense chemotherapy as much as possible.
2. For hormone receptor positive recurrent metastatic breast cancer with slow progression, postmenopausal patients may prefer endocrine therapy; premenopausal patients may choose chemotherapy or may also consider using ovarian function inhibition combined with other endocrine drugs.
3. For hormone receptor positive patients, endocrine therapy should be given promptly in the treatment gap when chemotherapy is ineffective and tumor is not controlled, or when the patient cannot tolerate continued chemotherapy for any reason. Patients with unknown hormone receptors or negative previous tests should also strive for endocrine therapy by determining the newly recurrent lesions or re-measuring the receptor results of previous lesions.
4. During the treatment phase, the criteria for evaluating the efficacy should be strict, based on the principle of “no change in formula if it is effective and no change if it is not effective”. After the failure of a certain treatment, we advocate the reasonable sequential use of chemotherapy and endocrine therapy. Different types of endocrine drugs can be applied sequentially in the relatively slow stage of disease development.
5. Long-term stability of disease after treatment is considered as clinical benefit for advanced stage patients.
For postmenopausal recurrent metastatic breast cancer, the first choice of first-line endocrine therapy is third-generation aromatase inhibitors, including anastrozole, letrozole and exemestane. International multicenter clinical studies have demonstrated that third-generation aromatase inhibitors are more effective than megestrol in the second-line treatment of recurrent metastatic breast cancer that has failed triamcinolone therapy. In first-line endocrine therapy for recurrent metastatic breast cancer, third-generation aromatase inhibitors are significantly more effective than triamcinolone. Chemotherapy may be preferred for premenopausal patients with recurrent metastatic breast cancer. If chemotherapy fails, or if the disease is suitable or requires endocrine therapy, pharmacologic ovarian debulking combined with aromatase inhibitors may be indicated.
The 2006 US NCCN Breast Cancer Treatment Guidelines have several clear definitions regarding the determination of menopause.
1, after bilateral oophorectomy (or effective radiation debulking).
2.Age 60 years or older.
3, age 60 years or younger, not receiving chemotherapy, triamcinolone acetonide, toremifene and treatment to suppress ovarian function, with more than 12 months of natural menopause and with blood E2 and FSH at postmenopausal levels.
4, aged 60 years or younger, treated with triamcinolone acetonide, toremifene, and with blood E2 and FSH reaching postmenopausal levels.
5, patients being treated with LH-RH analogues or agonists who are unable to determine whether they are menopausal.
6. Premenopausal women who are receiving adjuvant chemotherapy, menopause cannot be used as the basis for determining menopause.
After the failure of the preferred aromatase inhibitor treatment for recurrent metastatic breast cancer, chemotherapy can be considered; when it is suitable to continue with endocrine therapy, progestin, estrogen receptor modulator Fasolodex (fulvestrant), and other aromatase inhibitors can be chosen. And based on the lack of evidence from current clinical studies that there is no cross-resistance between third-generation aromatase inhibitors (inactivating), caution should be exercised when choosing another third-generation aromatase inhibitor after the failure of a particular aromatase inhibitor therapy.
In summary, for postmenopausal hormone receptor-positive patients, postoperative adjuvant endocrine therapy can be chosen from.
1. anastrozole or letrozole for 5 years postoperatively.
2, 2-3 years of triamcinolone followed by 2-3 years of sequential exemestane or anastrozole.
3. 5 years of triamcinolone followed by 5 years of intensive use of letrozole.
4. Patients who cannot tolerate aromatase inhibitor therapy for various reasons can still be treated with triamcinolone for 5 years.
In premenopausal hormone receptor-positive patients, postoperative adjuvant endocrine therapy can be chosen from.
1, start with triamcinolone acetonide for 2-3 years, and can be switched to aromatase inhibitors if they enter menopause.
2.If trimethoprim is still not menopausal after 2-3 years, trimethoprim can be continued until 5 years, and if it enters menopause after 5 years, then trimethoprim will be used for 5 years as follow-up intensive therapy.
3.For some premenopausal patients who are not suitable for treatment with triamcinolone, or who have high risk of recurrence and metastasis factors.